D-アミノ酸代謝酵素システムの機能と構造に関する疾患酸素学研究

概要

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D-Amino acid oxidase (DAO) has been proposed to be involved in the decreased glutamatergic neurotransmission in schizophrenia and the modulation of its activity is expected to be therapeutic. Here we show the inhibitory effect of antipsychotic drugs, chlorpromazine and risperidone, on human DAO activity. In search of the pathophysiological role of DAO, we analyzed its distribution in brain. The immunoreactivity for DAO was detected in glial cells of rhombencephalon and in choroid plexus (CP) in the human brain. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells. These results suggest that DAO expression level is altered in schizophrenia and the increase in DAO expression is involved in aberrant D-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid, and may be regarded as a potential therapeutic target for schizophrenia.
2012-02-25